CA3124702A1 - Fxr (nr1h4) modulating compounds - Google Patents
Fxr (nr1h4) modulating compounds Download PDFInfo
- Publication number
- CA3124702A1 CA3124702A1 CA3124702A CA3124702A CA3124702A1 CA 3124702 A1 CA3124702 A1 CA 3124702A1 CA 3124702 A CA3124702 A CA 3124702A CA 3124702 A CA3124702 A CA 3124702A CA 3124702 A1 CA3124702 A1 CA 3124702A1
- Authority
- CA
- Canada
- Prior art keywords
- fxr
- compound
- pharmaceutically acceptable
- acceptable salt
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 232
- 102100038495 Bile acid receptor Human genes 0.000 claims abstract description 117
- 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 claims abstract description 115
- 238000000034 method Methods 0.000 claims abstract description 66
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 51
- 238000011282 treatment Methods 0.000 claims abstract description 43
- 239000000556 agonist Substances 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 22
- 239000000203 mixture Substances 0.000 claims description 78
- 150000003839 salts Chemical class 0.000 claims description 69
- 239000003112 inhibitor Substances 0.000 claims description 55
- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 claims description 53
- 239000008194 pharmaceutical composition Substances 0.000 claims description 38
- 210000004185 liver Anatomy 0.000 claims description 34
- 208000019423 liver disease Diseases 0.000 claims description 22
- 108010075639 MAP Kinase Kinase Kinase 5 Proteins 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 20
- 230000001404 mediated effect Effects 0.000 claims description 19
- 102000004217 thyroid hormone receptors Human genes 0.000 claims description 18
- 108090000721 thyroid hormone receptors Proteins 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 16
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 14
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 13
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 13
- 230000001684 chronic effect Effects 0.000 claims description 12
- 102000000452 Acetyl-CoA carboxylase Human genes 0.000 claims description 11
- 108010016219 Acetyl-CoA carboxylase Proteins 0.000 claims description 11
- 108010018763 Biotin carboxylase Proteins 0.000 claims description 11
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 11
- 150000002632 lipids Chemical class 0.000 claims description 10
- 238000001757 thermogravimetry curve Methods 0.000 claims description 10
- 229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 claims description 9
- 230000001587 cholestatic effect Effects 0.000 claims description 9
- 208000010157 sclerosing cholangitis Diseases 0.000 claims description 8
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 8
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 7
- 206010016654 Fibrosis Diseases 0.000 claims description 6
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 6
- 230000000414 obstructive effect Effects 0.000 claims description 6
- 238000002411 thermogravimetry Methods 0.000 claims description 6
- 229940127254 ASK1 inhibitor Drugs 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 230000003176 fibrotic effect Effects 0.000 claims description 5
- 230000003463 hyperproliferative effect Effects 0.000 claims description 5
- 230000003211 malignant effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 4
- 208000004930 Fatty Liver Diseases 0.000 claims description 4
- 102000004895 Lipoproteins Human genes 0.000 claims description 4
- 108090001030 Lipoproteins Proteins 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
- 102100029152 UDP-glucuronosyltransferase 1A1 Human genes 0.000 claims description 4
- 101710205316 UDP-glucuronosyltransferase 1A1 Proteins 0.000 claims description 4
- 230000007882 cirrhosis Effects 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 206010000891 acute myocardial infarction Diseases 0.000 claims description 3
- 201000010897 colon adenocarcinoma Diseases 0.000 claims description 3
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
- 208000006454 hepatitis Diseases 0.000 claims description 3
- 231100000283 hepatitis Toxicity 0.000 claims description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 3
- 238000002271 resection Methods 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 2
- 238000002512 chemotherapy Methods 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 102100033127 Mitogen-activated protein kinase kinase kinase 5 Human genes 0.000 claims 4
- 238000002441 X-ray diffraction Methods 0.000 claims 4
- 208000007788 Acute Liver Failure Diseases 0.000 claims 1
- 206010000804 Acute hepatic failure Diseases 0.000 claims 1
- 208000023514 Barrett esophagus Diseases 0.000 claims 1
- 208000023665 Barrett oesophagus Diseases 0.000 claims 1
- 206010048832 Colon adenoma Diseases 0.000 claims 1
- 208000010334 End Stage Liver Disease Diseases 0.000 claims 1
- 208000011444 chronic liver failure Diseases 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 230000007774 longterm Effects 0.000 claims 1
- 230000001613 neoplastic effect Effects 0.000 claims 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 claims 1
- 208000015768 polyposis Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 40
- 238000002360 preparation method Methods 0.000 abstract description 31
- 230000015572 biosynthetic process Effects 0.000 abstract description 22
- 230000027455 binding Effects 0.000 abstract description 15
- 108020005497 Nuclear hormone receptor Proteins 0.000 abstract description 11
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 108020004017 nuclear receptors Proteins 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 5
- 102000006255 nuclear receptors Human genes 0.000 abstract 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 40
- 239000000243 solution Substances 0.000 description 36
- -1 amino, carbamyl Chemical group 0.000 description 33
- 230000000052 comparative effect Effects 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 102100031734 Fibroblast growth factor 19 Human genes 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 101000846394 Homo sapiens Fibroblast growth factor 19 Proteins 0.000 description 30
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 25
- 238000001990 intravenous administration Methods 0.000 description 23
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 description 23
- 230000002829 reductive effect Effects 0.000 description 22
- 239000000523 sample Substances 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000003446 ligand Substances 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- 238000000634 powder X-ray diffraction Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- 102000011853 MAP Kinase Kinase Kinase 5 Human genes 0.000 description 16
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 230000008484 agonism Effects 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
- 230000004913 activation Effects 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 13
- 239000003613 bile acid Substances 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- 239000000543 intermediate Substances 0.000 description 13
- 238000011321 prophylaxis Methods 0.000 description 13
- 239000002253 acid Substances 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 239000000651 prodrug Substances 0.000 description 12
- 229940002612 prodrug Drugs 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 230000014509 gene expression Effects 0.000 description 11
- 108020001756 ligand binding domains Proteins 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 241000282567 Macaca fascicularis Species 0.000 description 10
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 10
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 239000002002 slurry Substances 0.000 description 10
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000007513 acids Chemical class 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 230000009286 beneficial effect Effects 0.000 description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 9
- 229910052805 deuterium Inorganic materials 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- 230000000968 intestinal effect Effects 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 230000009885 systemic effect Effects 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 235000019253 formic acid Nutrition 0.000 description 8
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 7
- 239000008186 active pharmaceutical agent Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 235000001968 nicotinic acid Nutrition 0.000 description 7
- 239000011664 nicotinic acid Substances 0.000 description 7
- 230000036470 plasma concentration Effects 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- KPWYNAGOBXLMSE-UHFFFAOYSA-N Tipelukast Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1SCCCOC1=CC=C(C(C)=O)C(OCCCC(O)=O)=C1CCC KPWYNAGOBXLMSE-UHFFFAOYSA-N 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000007758 minimum essential medium Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229960003512 nicotinic acid Drugs 0.000 description 6
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical class N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 6
- 239000012453 solvate Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 150000003626 triacylglycerols Chemical class 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- 206010008635 Cholestasis Diseases 0.000 description 5
- 102000009666 Cytochrome P-450 CYP2B6 Human genes 0.000 description 5
- 108010020070 Cytochrome P-450 CYP2B6 Proteins 0.000 description 5
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 description 5
- 108090000376 Fibroblast growth factor 21 Proteins 0.000 description 5
- 102100025353 G-protein coupled bile acid receptor 1 Human genes 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 102100027159 Membrane primary amine oxidase Human genes 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 210000000941 bile Anatomy 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 201000001883 cholelithiasis Diseases 0.000 description 5
- 231100000359 cholestasis Toxicity 0.000 description 5
- 230000007870 cholestasis Effects 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 210000000936 intestine Anatomy 0.000 description 5
- 229940098779 methanesulfonic acid Drugs 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000013456 study Methods 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 102100039556 Galectin-4 Human genes 0.000 description 4
- 108010024636 Glutathione Proteins 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 101710132836 Membrane primary amine oxidase Proteins 0.000 description 4
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- WJVUSZOUINARJY-UHFFFAOYSA-N azetidin-3-ol Chemical compound N1CC(C1)O.N1CC(C1)O WJVUSZOUINARJY-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 208000001130 gallstones Diseases 0.000 description 4
- 229960003180 glutathione Drugs 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 210000001853 liver microsome Anatomy 0.000 description 4
- 229910001629 magnesium chloride Inorganic materials 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 230000003285 pharmacodynamic effect Effects 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 4
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 230000004580 weight loss Effects 0.000 description 4
- 108010011376 AMP-Activated Protein Kinases Proteins 0.000 description 3
- 102000014156 AMP-Activated Protein Kinases Human genes 0.000 description 3
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 3
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 3
- 102100020683 Beta-klotho Human genes 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 3
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 3
- KRSXWFQIZOXHPX-XTWYBNIISA-N CC(C)C[C@H](NC(=O)[C@@H](NC(=O)[C@@H]1CSSC[C@H](NC(C)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(N)=O Chemical compound CC(C)C[C@H](NC(=O)[C@@H](NC(=O)[C@@H]1CSSC[C@H](NC(C)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(N)=O KRSXWFQIZOXHPX-XTWYBNIISA-N 0.000 description 3
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 3
- 102000012234 Cannabinoid receptor type 1 Human genes 0.000 description 3
- 108050002726 Cannabinoid receptor type 1 Proteins 0.000 description 3
- 102000019034 Chemokines Human genes 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- XBUXXJUEBFDQHD-NHCUHLMSSA-N ClC1=C(C=CC(=C1)OCC=1C(=NOC1C1CC1)C1=C(C=CC=C1Cl)Cl)[C@@H]1[C@H](C1)C1=CC=C(C(=O)O)C=C1 Chemical compound ClC1=C(C=CC(=C1)OCC=1C(=NOC1C1CC1)C1=C(C=CC=C1Cl)Cl)[C@@H]1[C@H](C1)C1=CC=C(C(=O)O)C=C1 XBUXXJUEBFDQHD-NHCUHLMSSA-N 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 3
- 108010000561 Cytochrome P-450 CYP2C8 Proteins 0.000 description 3
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 3
- 102100029359 Cytochrome P450 2C8 Human genes 0.000 description 3
- 102100039205 Cytochrome P450 3A4 Human genes 0.000 description 3
- BYTNEISLBIENSA-MDZDMXLPSA-N GW 4064 Chemical compound CC(C)C=1ON=C(C=2C(=CC=CC=2Cl)Cl)C=1COC(C=C1Cl)=CC=C1\C=C\C1=CC=CC(C(O)=O)=C1 BYTNEISLBIENSA-MDZDMXLPSA-N 0.000 description 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
- 101001018196 Homo sapiens Mitogen-activated protein kinase kinase kinase 5 Proteins 0.000 description 3
- 206010022489 Insulin Resistance Diseases 0.000 description 3
- 108700023649 KBP-042 Proteins 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 3
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000003251 Pruritus Diseases 0.000 description 3
- 108091006269 SLC5A2 Proteins 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 102000058081 Sodium-Glucose Transporter 2 Human genes 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229960005370 atorvastatin Drugs 0.000 description 3
- 229950010015 bertilimumab Drugs 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000002559 chemokine receptor antagonist Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 230000001627 detrimental effect Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000012149 elution buffer Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000002443 hepatoprotective effect Effects 0.000 description 3
- 102000057989 human MAP3K5 Human genes 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 3
- 102000004311 liver X receptors Human genes 0.000 description 3
- 108090000865 liver X receptors Proteins 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002206 pro-fibrotic effect Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229940044601 receptor agonist Drugs 0.000 description 3
- 239000000018 receptor agonist Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000003419 tautomerization reaction Methods 0.000 description 3
- VMKIXWAFFVLJCK-UHFFFAOYSA-N tert-butyl 3-oxoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(=O)C1 VMKIXWAFFVLJCK-UHFFFAOYSA-N 0.000 description 3
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical class [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 229950004996 tipelukast Drugs 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 2
- QKDRXGFQVGOQKS-CRSSMBPESA-N (2s,3r,4r,5s,6r)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyloxane-3,4,5-triol Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](SC)O2)O)=CC=C1Cl QKDRXGFQVGOQKS-CRSSMBPESA-N 0.000 description 2
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 2
- SCVHJVCATBPIHN-SJCJKPOMSA-N (3s)-3-[[(2s)-2-[[2-(2-tert-butylanilino)-2-oxoacetyl]amino]propanoyl]amino]-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound N([C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)COC=1C(=C(F)C=C(F)C=1F)F)C(=O)C(=O)NC1=CC=CC=C1C(C)(C)C SCVHJVCATBPIHN-SJCJKPOMSA-N 0.000 description 2
- PPUXXDKQNAHHON-BJLQDIEVSA-N (3s)-n-cyclopropyl-3-[[(2r)-3-(cyclopropylmethylsulfonyl)-2-[[(1s)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]amino]propanoyl]amino]-2-oxopentanamide Chemical compound C([C@@H](C(=O)N[C@@H](CC)C(=O)C(=O)NC1CC1)N[C@@H](C=1C=CC(F)=CC=1)C(F)(F)F)S(=O)(=O)CC1CC1 PPUXXDKQNAHHON-BJLQDIEVSA-N 0.000 description 2
- SHKXZIQNFMOPBS-OOMQYRRCSA-N (4r)-4-[(3s,5s,7r,8r,9s,10s,12s,13r,14s,17r)-7,12-dihydroxy-3-(icosanoylamino)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoic acid Chemical compound O[C@H]1C[C@@H]2[C@@]3(C)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC)C[C@H]3C[C@@H](O)[C@H]2[C@@H]2CC[C@H]([C@H](C)CCC(O)=O)[C@]21C SHKXZIQNFMOPBS-OOMQYRRCSA-N 0.000 description 2
- HYAFETHFCAUJAY-VHLRUQIKSA-N (5r)-5-deuterio-5-[[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C=1C=C(OCCC=2N=CC(CC)=CC=2)C=CC=1C[C@@]1([2H])SC(=O)NC1=O HYAFETHFCAUJAY-VHLRUQIKSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 2
- NPLISPOULZRKEC-UHFFFAOYSA-N 2,6-dichloro-4-fluoro-N-hydroxybenzenecarboximidoyl chloride Chemical compound ClC1=C(C(=NO)Cl)C(=CC(=C1)F)Cl NPLISPOULZRKEC-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- JWHYSEDOYMYMNM-QGZVFWFLSA-N 2-[4-[(2r)-2-ethoxy-3-[4-(trifluoromethyl)phenoxy]propyl]sulfanyl-2-methylphenoxy]acetic acid Chemical compound C([C@@H](OCC)CSC=1C=C(C)C(OCC(O)=O)=CC=1)OC1=CC=C(C(F)(F)F)C=C1 JWHYSEDOYMYMNM-QGZVFWFLSA-N 0.000 description 2
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 2
- BZUUVQCSPHPUQA-UHFFFAOYSA-N 2-bromo-5-chloropyridine Chemical compound ClC1=CC=C(Br)N=C1 BZUUVQCSPHPUQA-UHFFFAOYSA-N 0.000 description 2
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 2
- BQMMCRXYIIKAOB-UHFFFAOYSA-N 3-[6-chloro-2-cyclopropyl-1-(1-ethylpyrazol-4-yl)-7-fluoroindol-3-yl]sulfanyl-2-fluorobenzoic acid Chemical compound ClC1=CC=C2C(=C(N(C2=C1F)C=1C=NN(C1)CC)C1CC1)SC=1C(=C(C(=O)O)C=CC1)F BQMMCRXYIIKAOB-UHFFFAOYSA-N 0.000 description 2
- QNKMXCMJVQFBLM-UHFFFAOYSA-N 3-[6-chloro-7-fluoro-2-methyl-1-(1-propylpyrazol-4-yl)indol-3-yl]sulfanyl-2-fluorobenzoic acid Chemical compound C1=NN(CCC)C=C1N1C2=C(F)C(Cl)=CC=C2C(SC=2C(=C(C(O)=O)C=CC=2)F)=C1C QNKMXCMJVQFBLM-UHFFFAOYSA-N 0.000 description 2
- OQDQIFQRNZIEEJ-UHFFFAOYSA-N 4-[1-(1,3-benzothiazol-6-ylsulfonyl)-5-chloroindol-2-yl]butanoic acid Chemical compound C1=C2N=CSC2=CC(S(=O)(=O)N2C3=CC=C(Cl)C=C3C=C2CCCC(=O)O)=C1 OQDQIFQRNZIEEJ-UHFFFAOYSA-N 0.000 description 2
- BBGOSBDSLYHMRA-UHFFFAOYSA-N 4-[1-[4-cyclobutyl-2-methyl-5-(5-methyl-1h-1,2,4-triazol-3-yl)benzoyl]piperidin-4-yl]benzonitrile Chemical compound N1C(C)=NN=C1C1=CC(C(=O)N2CCC(CC2)C=2C=CC(=CC=2)C#N)=C(C)C=C1C1CCC1 BBGOSBDSLYHMRA-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- LGGPZDRLTDGYSQ-JADSYQMUSA-N 4-[[4-[[(2r,4s)-4-(3-chlorophenyl)-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl]methoxy]-2,6-dimethylphenyl]methyl]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(CC=2C(=CC(OC[P@]3(=O)O[C@@H](CCO3)C=3C=C(Cl)C=CC=3)=CC=2C)C)=C1 LGGPZDRLTDGYSQ-JADSYQMUSA-N 0.000 description 2
- SDDSJMXGJNWMJY-BRHAQHMBSA-N 7-[(2r,4ar,5r,7ar)-2-[(3s)-1,1-difluoro-3-methylpentyl]-2-hydroxy-6-oxo-3,4,4a,5,7,7a-hexahydrocyclopenta[b]pyran-5-yl]heptanoic acid Chemical compound O1[C@](C(F)(F)C[C@@H](C)CC)(O)CC[C@@H]2[C@@H](CCCCCCC(O)=O)C(=O)C[C@H]21 SDDSJMXGJNWMJY-BRHAQHMBSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 101710159293 Acyl-CoA desaturase 1 Proteins 0.000 description 2
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 2
- 108010028700 Amine Oxidase (Copper-Containing) Proteins 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108070000005 Bile acid receptors Proteins 0.000 description 2
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 2
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 2
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 2
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 2
- PAOANWZGLPPROA-RQXXJAGISA-N CGS-21680 Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(NCCC=3C=CC(CCC(O)=O)=CC=3)=NC(N)=C2N=C1 PAOANWZGLPPROA-RQXXJAGISA-N 0.000 description 2
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 2
- AEMZEDNMNLIDSL-YGCVIUNWSA-N Cl.CC(C)(C)NC(=O)C1=CC=C(OC\C(CN)=C\F)C=C1 Chemical compound Cl.CC(C)(C)NC(=O)C1=CC=C(OC\C(CN)=C\F)C=C1 AEMZEDNMNLIDSL-YGCVIUNWSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 208000009011 Cytochrome P-450 CYP3A Inhibitors Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 2
- 102100035762 Diacylglycerol O-acyltransferase 2 Human genes 0.000 description 2
- 101710167503 Diacylglycerol O-acyltransferase 2 Proteins 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 description 2
- 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 description 2
- 108050004000 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 description 2
- 108010061435 Enalapril Proteins 0.000 description 2
- 102100023688 Eotaxin Human genes 0.000 description 2
- 101710139422 Eotaxin Proteins 0.000 description 2
- MCIACXAZCBVDEE-CUUWFGFTSA-N Ertugliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@@]23O[C@@](CO)(CO2)[C@@H](O)[C@H](O)[C@H]3O)=CC=C1Cl MCIACXAZCBVDEE-CUUWFGFTSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010039731 Fatty Acid Synthases Proteins 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 108010001515 Galectin 4 Proteins 0.000 description 2
- 206010017943 Gastrointestinal conditions Diseases 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 229920002527 Glycogen Polymers 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- 239000007821 HATU Substances 0.000 description 2
- 108010055039 HSP47 Heat-Shock Proteins Proteins 0.000 description 2
- 102100022054 Hepatocyte nuclear factor 4-alpha Human genes 0.000 description 2
- 101001139095 Homo sapiens Beta-klotho Proteins 0.000 description 2
- 101000857733 Homo sapiens G-protein coupled bile acid receptor 1 Proteins 0.000 description 2
- 101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 2
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 description 2
- 101710125793 Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 229940126032 IVA-337 Drugs 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 229940122355 Insulin sensitizer Drugs 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 102100023418 Ketohexokinase Human genes 0.000 description 2
- 108010062852 Ketohexokinase Proteins 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 241000254158 Lampyridae Species 0.000 description 2
- LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 2
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 2
- 102100022119 Lipoprotein lipase Human genes 0.000 description 2
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 2
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 2
- 108010019598 Liraglutide Proteins 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 102100021948 Lysyl oxidase homolog 2 Human genes 0.000 description 2
- 101710183215 Lysyl oxidase homolog 2 Proteins 0.000 description 2
- 108010072388 Methyl-CpG-Binding Protein 2 Proteins 0.000 description 2
- 102100039124 Methyl-CpG-binding protein 2 Human genes 0.000 description 2
- 102000047918 Myelin Basic Human genes 0.000 description 2
- 101710107068 Myelin basic protein Proteins 0.000 description 2
- AIEJNILLTCAQTJ-UHFFFAOYSA-N N-[(2,6-dichloro-4-fluorophenyl)methylidene]hydroxylamine Chemical compound ClC1=C(C=NO)C(=CC(=C1)F)Cl AIEJNILLTCAQTJ-UHFFFAOYSA-N 0.000 description 2
- 229940123857 NADPH oxidase inhibitor Drugs 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- WJBLNOPPDWQMCH-MBPVOVBZSA-N Nalmefene Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 WJBLNOPPDWQMCH-MBPVOVBZSA-N 0.000 description 2
- VYLOOGHLKSNNEK-PIIMJCKOSA-N OC(=O)c1cc(F)c2nc(sc2c1)N1[C@H]2CC[C@@H]1C[C@@H](C2)OCc1c(onc1-c1ccccc1OC(F)(F)F)C1CC1 Chemical compound OC(=O)c1cc(F)c2nc(sc2c1)N1[C@H]2CC[C@@H]1C[C@@H](C2)OCc1c(onc1-c1ccccc1OC(F)(F)F)C1CC1 VYLOOGHLKSNNEK-PIIMJCKOSA-N 0.000 description 2
- 239000012124 Opti-MEM Substances 0.000 description 2
- 102000017491 P2Y13 purinoceptor Human genes 0.000 description 2
- 108050005708 P2Y13 purinoceptor Proteins 0.000 description 2
- 108091008606 PDGF receptors Proteins 0.000 description 2
- 108700027412 Pegbelfermin Proteins 0.000 description 2
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 2
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 2
- 229940118430 Protease-activated receptor-2 antagonist Drugs 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 2
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical compound CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 description 2
- 102100027287 Serpin H1 Human genes 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 108010020396 Sterol Regulatory Element Binding Proteins Proteins 0.000 description 2
- 102000009822 Sterol Regulatory Element Binding Proteins Human genes 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- PIUZYOCNZPYXOA-ZHHJOTBYSA-N [(3s,8s,9s,10r,13r,14s,17r)-17-[(2r)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] hydrogen sulfate Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCCC(C)(C)O)C)[C@@]1(C)CC2 PIUZYOCNZPYXOA-ZHHJOTBYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229950006993 alipogene tiparvovec Drugs 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000002202 anti-cholestatic effect Effects 0.000 description 2
- 230000003510 anti-fibrotic effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 210000000013 bile duct Anatomy 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- PNDKCRDVVKJPKG-WHERJAGFSA-N cenicriviroc Chemical compound C1=CC(OCCOCCCC)=CC=C1C1=CC=C(N(CC(C)C)CCC\C(=C/2)C(=O)NC=3C=CC(=CC=3)[S@@](=O)CC=3N(C=NC=3)CCC)C\2=C1 PNDKCRDVVKJPKG-WHERJAGFSA-N 0.000 description 2
- 229950011033 cenicriviroc Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003467 chloride channel stimulating agent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229950005980 cobiprostone Drugs 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 2
- 229960003834 dapagliflozin Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 235000013367 dietary fats Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000036267 drug metabolism Effects 0.000 description 2
- 229950000234 emricasan Drugs 0.000 description 2
- 229960000873 enalapril Drugs 0.000 description 2
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 2
- 229950006535 ertugliflozin Drugs 0.000 description 2
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229960003765 fluvastatin Drugs 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- AFLFKFHDSCQHOL-IZZDOVSWSA-N gft505 Chemical compound C1=CC(SC)=CC=C1C(=O)\C=C\C1=CC(C)=C(OC(C)(C)C(O)=O)C(C)=C1 AFLFKFHDSCQHOL-IZZDOVSWSA-N 0.000 description 2
- 230000004110 gluconeogenesis Effects 0.000 description 2
- 229930182480 glucuronide Natural products 0.000 description 2
- 150000008134 glucuronides Chemical class 0.000 description 2
- 229940096919 glycogen Drugs 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- AHFWIQIYAXSLBA-RQXATKFSSA-N ipragliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(F)C(CC=2SC3=CC=CC=C3C=2)=C1 AHFWIQIYAXSLBA-RQXATKFSSA-N 0.000 description 2
- 229950000991 ipragliflozin Drugs 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- 230000000155 isotopic effect Effects 0.000 description 2
- 229960004125 ketoconazole Drugs 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960002397 linagliptin Drugs 0.000 description 2
- 229960002701 liraglutide Drugs 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 101150062900 lpl gene Proteins 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229960003151 mercaptamine Drugs 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- QNTASHOAVRSLMD-FCARAQADSA-N olesoxime Chemical compound C1CC2=C\C(=N/O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 QNTASHOAVRSLMD-FCARAQADSA-N 0.000 description 2
- 229950001051 olesoxime Drugs 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 229940100692 oral suspension Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 239000004031 partial agonist Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 108091012330 pegilodecakin Proteins 0.000 description 2
- 229950007092 pegilodecakin Drugs 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 2
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- 229960005095 pioglitazone Drugs 0.000 description 2
- 229960002797 pitavastatin Drugs 0.000 description 2
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000002600 positron emission tomography Methods 0.000 description 2
- CJMKTEIIPMBTJB-DXFHJFHKSA-M potassium;[(2r,3r,4s,5r,6r)-6-[[3-[(3s,4r,5r)-3-butyl-7-(dimethylamino)-3-ethyl-4-hydroxy-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-5-yl]phenyl]carbamoylamino]-3,5-dihydroxy-4-phenylmethoxyoxan-2-yl]methyl sulfate Chemical compound [K+].O([C@H]1[C@H](O)[C@@H](COS([O-])(=O)=O)O[C@H]([C@@H]1O)NC(=O)NC=1C=CC=C(C=1)[C@@H]1C2=CC(=CC=C2S(=O)(=O)C[C@@]([C@@H]1O)(CC)CCCC)N(C)C)CC1=CC=CC=C1 CJMKTEIIPMBTJB-DXFHJFHKSA-M 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 229960002965 pravastatin Drugs 0.000 description 2
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- XEABSBMNTNXEJM-UHFFFAOYSA-N propagermanium Chemical compound OC(=O)CC[Ge](=O)O[Ge](=O)CCC(O)=O XEABSBMNTNXEJM-UHFFFAOYSA-N 0.000 description 2
- 229950002828 propagermanium Drugs 0.000 description 2
- 230000004952 protein activity Effects 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 239000003909 protein kinase inhibitor Substances 0.000 description 2
- 229940076155 protein modulator Drugs 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 239000003227 purinergic agonist Substances 0.000 description 2
- 125000005551 pyridylene group Chemical group 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 229940075993 receptor modulator Drugs 0.000 description 2
- 229950011516 remogliflozin etabonate Drugs 0.000 description 2
- UAOCLDQAQNNEAX-ABMICEGHSA-N remogliflozin etabonate Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](COC(=O)OCC)O[C@H]1OC1=NN(C(C)C)C(C)=C1CC1=CC=C(OC(C)C)C=C1 UAOCLDQAQNNEAX-ABMICEGHSA-N 0.000 description 2
- FDBYIYFVSAHJLY-UHFFFAOYSA-N resmetirom Chemical compound N1C(=O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)N2C(NC(=O)C(C#N)=N2)=O)Cl)=N1 FDBYIYFVSAHJLY-UHFFFAOYSA-N 0.000 description 2
- 229960000672 rosuvastatin Drugs 0.000 description 2
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- MRWFZSLZNUJVQW-DEOSSOPVSA-N saroglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCN1C(C=2C=CC(SC)=CC=2)=CC=C1C MRWFZSLZNUJVQW-DEOSSOPVSA-N 0.000 description 2
- 229950006544 saroglitazar Drugs 0.000 description 2
- 229950011186 semaglutide Drugs 0.000 description 2
- 108010060325 semaglutide Proteins 0.000 description 2
- RGYQPQARIQKJKH-UHFFFAOYSA-N setanaxib Chemical compound CN(C)C1=CC=CC(C2=C3C(=O)N(C=4C(=CC=CC=4)Cl)NC3=CC(=O)N2C)=C1 RGYQPQARIQKJKH-UHFFFAOYSA-N 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 229960003310 sildenafil Drugs 0.000 description 2
- 229950009513 simtuzumab Drugs 0.000 description 2
- 229960002855 simvastatin Drugs 0.000 description 2
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
- 238000002603 single-photon emission computed tomography Methods 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 229940054269 sodium pyruvate Drugs 0.000 description 2
- 108010003524 sodium-bile acid cotransporter Proteins 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 229950005268 sotagliflozin Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229960003080 taurine Drugs 0.000 description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- IXXFZUPTQVDPPK-ZAWHAJPISA-N (1r,2r,4r,6r,7r,8r,10s,13r,14s)-17-[4-[4-(3-aminophenyl)triazol-1-yl]butyl]-7-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-13-ethyl-10-fluoro-6-methoxy-2,4,6,8,10,14-hexamethyl-12,15-dioxa-17-azabicyclo[12.3.0]heptadecane-3,9,11,16-tet Chemical compound O([C@@H]1[C@@H](C)C(=O)[C@](C)(F)C(=O)O[C@@H]([C@]2(OC(=O)N(CCCCN3N=NC(=C3)C=3C=C(N)C=CC=3)[C@@H]2[C@@H](C)C(=O)[C@H](C)C[C@@]1(C)OC)C)CC)[C@@H]1O[C@H](C)C[C@H](N(C)C)[C@H]1O IXXFZUPTQVDPPK-ZAWHAJPISA-N 0.000 description 1
- NPBCMXATLRCCLF-IRRLEISYSA-N (2s,4r)-4-[(3r,5s,6r,7r,8r,9s,10s,12s,13r,14s,17r)-6-ethyl-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2C[C@H](O)[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 NPBCMXATLRCCLF-IRRLEISYSA-N 0.000 description 1
- JMSUDQYHPSNBSN-UHFFFAOYSA-N (3,5-dichlorophenyl)methyl 4-[3-oxo-3-(2-oxo-3h-1,3-benzoxazol-6-yl)propyl]piperazine-1-carboxylate Chemical compound ClC1=CC(Cl)=CC(COC(=O)N2CCN(CCC(=O)C=3C=C4OC(=O)NC4=CC=3)CC2)=C1 JMSUDQYHPSNBSN-UHFFFAOYSA-N 0.000 description 1
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- QYYDXDSPYPOWRO-JHMCBHKWSA-N (3r)-3-[(3r,5s,7s,8r,9s,10s,13r,14s,17r)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]butanoic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CC(O)=O)C)[C@@]2(C)CC1 QYYDXDSPYPOWRO-JHMCBHKWSA-N 0.000 description 1
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
- ZROLHBHDLIHEMS-HUUCEWRRSA-N (6ar,10ar)-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCC)=CC(O)=C3[C@@H]21 ZROLHBHDLIHEMS-HUUCEWRRSA-N 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- NETTXQJYJRFTFS-UHFFFAOYSA-N 1-(4-hydroxyphenyl)-5-methylpyridin-2-one Chemical compound C1=C(C)C=CC(=O)N1C1=CC=C(O)C=C1 NETTXQJYJRFTFS-UHFFFAOYSA-N 0.000 description 1
- SJKLCUGQVVYDCX-HRNVLBFRSA-N 1-(4-tert-butylphenyl)sulfonyl-3-[(3R)-3-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]butyl]urea Chemical compound CC[C@H]1[C@@H](O)[C@H]2[C@@H]3CC[C@H]([C@H](C)CCNC(=O)NS(=O)(=O)c4ccc(cc4)C(C)(C)C)[C@@]3(C)CC[C@@H]2[C@@]2(C)CC[C@@H](O)C[C@@H]12 SJKLCUGQVVYDCX-HRNVLBFRSA-N 0.000 description 1
- GQBRZBHEPUQRPL-LJQANCHMSA-N 1-[4-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 GQBRZBHEPUQRPL-LJQANCHMSA-N 0.000 description 1
- YLFRRPUBVUAHSR-RRPFGEQOSA-N 16,17-didehydropregnenolone Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC=C(C(=O)C)[C@@]1(C)CC2 YLFRRPUBVUAHSR-RRPFGEQOSA-N 0.000 description 1
- YLFRRPUBVUAHSR-UHFFFAOYSA-N 16-dehydro-pregnenolone Natural products C1C=C2CC(O)CCC2(C)C2C1C1CC=C(C(=O)C)C1(C)CC2 YLFRRPUBVUAHSR-UHFFFAOYSA-N 0.000 description 1
- MUOHJTRCBBDUOW-QXYWQCSFSA-N 17beta-estradiol 3-glucosiduronic acid Chemical compound C([C@@H]1[C@@H](C2=CC=3)CC[C@]4([C@H]1CC[C@@H]4O)C)CC2=CC=3O[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O MUOHJTRCBBDUOW-QXYWQCSFSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- UOQMGQYMDHYXTB-UHFFFAOYSA-N 2,6-dichloro-4-fluorobenzaldehyde Chemical compound FC1=CC(Cl)=C(C=O)C(Cl)=C1 UOQMGQYMDHYXTB-UHFFFAOYSA-N 0.000 description 1
- VTAKZNRDSPNOAU-UHFFFAOYSA-M 2-(chloromethyl)oxirane;hydron;prop-2-en-1-amine;n-prop-2-enyldecan-1-amine;trimethyl-[6-(prop-2-enylamino)hexyl]azanium;dichloride Chemical compound Cl.[Cl-].NCC=C.ClCC1CO1.CCCCCCCCCCNCC=C.C[N+](C)(C)CCCCCCNCC=C VTAKZNRDSPNOAU-UHFFFAOYSA-M 0.000 description 1
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
- HNAJDMYOTDNOBK-UHFFFAOYSA-N 2-[2-[2-(2,6-dichlorophenyl)propan-2-yl]-1-[2-fluoro-4-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]imidazol-4-yl]propan-2-ol Chemical compound N=1C(C(C)(O)C)=CN(C=2C(=CC(=CC=2)C=2C=C(C(CO)=C(F)C=2)S(C)(=O)=O)F)C=1C(C)(C)C1=C(Cl)C=CC=C1Cl HNAJDMYOTDNOBK-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- BGDYLOGCMJAUHR-UHFFFAOYSA-N 2-chloro-3-fluoro-6-methylpyridine Chemical compound CC1=CC=C(F)C(Cl)=N1 BGDYLOGCMJAUHR-UHFFFAOYSA-N 0.000 description 1
- CZGVOBIGEBDYTP-VSGBNLITSA-N 3-[[(3r,5r)-3-butyl-3-ethyl-7-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},4-benzothiazepin-8-yl]methylamino]pentanedioic acid Chemical compound C1([C@@H]2C3=CC(OC)=C(CNC(CC(O)=O)CC(O)=O)C=C3S(=O)(=O)C[C@@](N2)(CC)CCCC)=CC=CC=C1 CZGVOBIGEBDYTP-VSGBNLITSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- XBUXXJUEBFDQHD-UHFFFAOYSA-N 4-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]cyclopropyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1C(C=2C(=CC(OCC=3C(=NOC=3C3CC3)C=3C(=CC=CC=3Cl)Cl)=CC=2)Cl)C1 XBUXXJUEBFDQHD-UHFFFAOYSA-N 0.000 description 1
- FQEYHIPPYOSPLF-UHFFFAOYSA-N 4-bromo-3-chlorophenol Chemical compound OC1=CC=C(Br)C(Cl)=C1 FQEYHIPPYOSPLF-UHFFFAOYSA-N 0.000 description 1
- 229940124125 5 Lipoxygenase inhibitor Drugs 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- SDMBRCRVFFHJKR-UHFFFAOYSA-N 6-(5-carboxy-5-methylhexoxy)-2,2-dimethylhexanoic acid Chemical compound OC(=O)C(C)(C)CCCCOCCCCC(C)(C)C(O)=O SDMBRCRVFFHJKR-UHFFFAOYSA-N 0.000 description 1
- RPVDFHPBGBMWID-UHFFFAOYSA-N 6-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]piperidin-1-yl]-1-methylindole-3-carboxylic acid Chemical compound C1=C2N(C)C=C(C(O)=O)C2=CC=C1N(CC1)CCC1OCC1=C(C2CC2)ON=C1C1=C(Cl)C=CC=C1Cl RPVDFHPBGBMWID-UHFFFAOYSA-N 0.000 description 1
- 230000035502 ADME Effects 0.000 description 1
- 229940122216 Adenosine A3 receptor agonist Drugs 0.000 description 1
- 102000003808 Adiponectin Receptors Human genes 0.000 description 1
- 108090000179 Adiponectin Receptors Proteins 0.000 description 1
- 229940124232 Adiponectin receptor agonist Drugs 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 108010009551 Alamethicin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 229940124035 Amylin receptor agonist Drugs 0.000 description 1
- 102400000345 Angiotensin-2 Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 238000013258 ApoE Receptor knockout mouse model Methods 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 description 1
- 108010019625 Atazanavir Sulfate Proteins 0.000 description 1
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 101710104526 Beta-klotho Proteins 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- GAVGYRAGBGVASR-UHFFFAOYSA-N BrC1=C(C=C(O[Si](C)(C)C(C)(C)C)C=C1)Cl Chemical compound BrC1=C(C=C(O[Si](C)(C)C(C)(C)C)C=C1)Cl GAVGYRAGBGVASR-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 101100135867 Caenorhabditis elegans pde-3 gene Proteins 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108010001789 Calcitonin Receptors Proteins 0.000 description 1
- 102100038520 Calcitonin receptor Human genes 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000003952 Caspase 3 Human genes 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 229940123169 Caspase inhibitor Drugs 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 229940123003 Cathepsin inhibitor Drugs 0.000 description 1
- 102000005600 Cathepsins Human genes 0.000 description 1
- 108010084457 Cathepsins Proteins 0.000 description 1
- 102000003727 Caveolin 1 Human genes 0.000 description 1
- 108090000026 Caveolin 1 Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 229920002905 Colesevelam Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000035984 Colonic Polyps Diseases 0.000 description 1
- 206010056533 Congenital hepatic fibrosis Diseases 0.000 description 1
- 102000008954 Copper amine oxidases Human genes 0.000 description 1
- 208000014997 Crohn colitis Diseases 0.000 description 1
- 108010058546 Cyclin D1 Proteins 0.000 description 1
- 208000006075 Cytochrome P-450 CYP2B6 Inhibitors Diseases 0.000 description 1
- 208000005487 Cytochrome P-450 CYP2C9 Inhibitors Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102100038637 Cytochrome P450 7A1 Human genes 0.000 description 1
- 101710176143 Cytochrome P450 7A1 Proteins 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102100036869 Diacylglycerol O-acyltransferase 1 Human genes 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102100023275 Dual specificity mitogen-activated protein kinase kinase 3 Human genes 0.000 description 1
- 102100023401 Dual specificity mitogen-activated protein kinase kinase 6 Human genes 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102100038083 Endosialin Human genes 0.000 description 1
- 101710144543 Endosialin Proteins 0.000 description 1
- 102400000686 Endothelin-1 Human genes 0.000 description 1
- 101800004490 Endothelin-1 Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102100038595 Estrogen receptor Human genes 0.000 description 1
- LCDDAGSJHKEABN-MLGOLLRUSA-N Evogliptin Chemical compound C1CNC(=O)[C@@H](COC(C)(C)C)N1C(=O)C[C@H](N)CC1=CC(F)=C(F)C=C1F LCDDAGSJHKEABN-MLGOLLRUSA-N 0.000 description 1
- 208000030306 Eye degenerative disease Diseases 0.000 description 1
- VLQTUNDJHLEFEQ-KGENOOAVSA-N Fexaramine Chemical compound COC(=O)\C=C\C1=CC=CC(N(CC=2C=CC(=CC=2)C=2C=CC(=CC=2)N(C)C)C(=O)C2CCCCC2)=C1 VLQTUNDJHLEFEQ-KGENOOAVSA-N 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 1
- 101710153349 Fibroblast growth factor 19 Proteins 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 229940123497 G protein-coupled bile acid receptor 1 agonist Drugs 0.000 description 1
- 101710154531 G-protein coupled bile acid receptor 1 Proteins 0.000 description 1
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 108010001517 Galectin 3 Proteins 0.000 description 1
- 102100039558 Galectin-3 Human genes 0.000 description 1
- 229940126043 Galectin-3 inhibitor Drugs 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229940123232 Glucagon receptor agonist Drugs 0.000 description 1
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
- 229940127552 Glucagon-like Peptide-1 (GLP-1) Agonists Drugs 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 1
- 102100032882 Glucagon-like peptide 1 receptor Human genes 0.000 description 1
- 108010092364 Glucuronosyltransferase Proteins 0.000 description 1
- 102000016354 Glucuronosyltransferase Human genes 0.000 description 1
- 244000060234 Gmelina philippensis Species 0.000 description 1
- 238000012752 Hepatectomy Methods 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 108010086524 Hepatocyte Nuclear Factor 4 Proteins 0.000 description 1
- 101000927974 Homo sapiens Diacylglycerol O-acyltransferase 1 Proteins 0.000 description 1
- 101001115394 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 3 Proteins 0.000 description 1
- 101000624426 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 6 Proteins 0.000 description 1
- 229940127517 Hormone Receptor Modulators Drugs 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000032177 Intestinal Polyps Diseases 0.000 description 1
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
- 101150009057 JAK2 gene Proteins 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 102220470475 L-seryl-tRNA(Sec) kinase_C57L_mutation Human genes 0.000 description 1
- XXYGTCZJJLTAGH-UHFFFAOYSA-N LGK974 Chemical compound C1=NC(C)=CC(C=2C(=CC(CC(=O)NC=3N=CC(=CC=3)C=3N=CC=NC=3)=CN=2)C)=C1 XXYGTCZJJLTAGH-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010051589 Large intestine polyp Diseases 0.000 description 1
- 244000147568 Laurus nobilis Species 0.000 description 1
- 235000017858 Laurus nobilis Nutrition 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 229940127470 Lipase Inhibitors Drugs 0.000 description 1
- 229940086609 Lipase inhibitor Drugs 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 108091008065 MIR21 Proteins 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 102000000424 Matrix Metalloproteinase 2 Human genes 0.000 description 1
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 1
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
- 102100026262 Metalloproteinase inhibitor 2 Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102100023174 Methionine aminopeptidase 2 Human genes 0.000 description 1
- 229940122028 Methionine aminopeptidase-2 inhibitor Drugs 0.000 description 1
- 108090000192 Methionyl aminopeptidases Proteins 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101000878182 Mus musculus Fibroblast growth factor 15 Proteins 0.000 description 1
- 101100344292 Mus musculus Map3k5 gene Proteins 0.000 description 1
- 235000009421 Myristica fragrans Nutrition 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- CDSKRHGFXHZEQL-JOCHJYFZSA-N N1N=CC2=CC(=CC=C12)N1C(N(C(C12CCN(CC2)C([C@@H](C(C)C)NC(C2=C(C=CC(=C2)C(F)(F)F)F)=O)=O)=O)C)=O Chemical compound N1N=CC2=CC(=CC=C12)N1C(N(C(C12CCN(CC2)C([C@@H](C(C)C)NC(C2=C(C=CC(=C2)C(F)(F)F)F)=O)=O)=O)C)=O CDSKRHGFXHZEQL-JOCHJYFZSA-N 0.000 description 1
- 102000004019 NADPH Oxidase 1 Human genes 0.000 description 1
- 108090000424 NADPH Oxidase 1 Proteins 0.000 description 1
- 108010082699 NADPH Oxidase 4 Proteins 0.000 description 1
- 102100021872 NADPH oxidase 4 Human genes 0.000 description 1
- 102000034570 NR1 subfamily Human genes 0.000 description 1
- 108020001305 NR1 subfamily Proteins 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 108090001146 Nuclear Receptor Coactivator 1 Proteins 0.000 description 1
- 102100037223 Nuclear receptor coactivator 1 Human genes 0.000 description 1
- 102100028448 Nuclear receptor subfamily 2 group C member 2 Human genes 0.000 description 1
- 102100022669 Nuclear receptor subfamily 5 group A member 2 Human genes 0.000 description 1
- 101710105538 Nuclear receptor subfamily 5 group A member 2 Proteins 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 229940125819 PF-06835919 Drugs 0.000 description 1
- 108010028924 PPAR alpha Proteins 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 102000000536 PPAR gamma Human genes 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 229940122054 Peroxisome proliferator-activated receptor delta agonist Drugs 0.000 description 1
- 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 229940123263 Phosphodiesterase 3 inhibitor Drugs 0.000 description 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 1
- 229940124034 Phospholipase C inhibitor Drugs 0.000 description 1
- 241000254064 Photinus pyralis Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 208000037062 Polyps Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100040918 Pro-glucagon Human genes 0.000 description 1
- 208000017855 Progressive familial intrahepatic cholestasis type 1 Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 108010052090 Renilla Luciferases Proteins 0.000 description 1
- 241000242743 Renilla reniformis Species 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 108050002485 Sirtuin Proteins 0.000 description 1
- 102000011990 Sirtuin Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000005212 Terminalia tomentosa Nutrition 0.000 description 1
- 102100033451 Thyroid hormone receptor beta Human genes 0.000 description 1
- 229940123876 Thyroid hormone receptor beta agonist Drugs 0.000 description 1
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 1
- 108010031372 Tissue Inhibitor of Metalloproteinase-2 Proteins 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 229940122954 Transcription factor inhibitor Drugs 0.000 description 1
- 229940098113 Transglutaminase inhibitor Drugs 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- HDYANYHVCAPMJV-LXQIFKJMSA-N UDP-alpha-D-glucuronic acid Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C(NC(=O)C=C1)=O)O)O)OP(O)(=O)OP(O)(=O)O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O HDYANYHVCAPMJV-LXQIFKJMSA-N 0.000 description 1
- 108010020961 UGT1A1 enzyme Proteins 0.000 description 1
- HDYANYHVCAPMJV-UHFFFAOYSA-N Uridine diphospho-D-glucuronic acid Natural products O1C(N2C(NC(=O)C=C2)=O)C(O)C(O)C1COP(O)(=O)OP(O)(=O)OC1OC(C(O)=O)C(O)C(O)C1O HDYANYHVCAPMJV-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- XGIYOABXZNJOHV-APIYUPOTSA-N [(3r)-3-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]butyl] hydrogen sulfate Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)CCOS(O)(=O)=O)CC[C@H]21 XGIYOABXZNJOHV-APIYUPOTSA-N 0.000 description 1
- VHOZWHQPEJGPCC-AZXNYEMZSA-N [4-[[(6s,9s,9as)-1-(benzylcarbamoyl)-2,9-dimethyl-4,7-dioxo-8-(quinolin-8-ylmethyl)-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazin-6-yl]methyl]phenyl] dihydrogen phosphate Chemical compound C([C@@H]1N2[C@@H](N(N(C)CC2=O)C(=O)NCC=2C=CC=CC=2)[C@@H](N(C1=O)CC=1C2=NC=CC=C2C=CC=1)C)C1=CC=C(OP(O)(O)=O)C=C1 VHOZWHQPEJGPCC-AZXNYEMZSA-N 0.000 description 1
- UTQCHRYALQNQDS-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC1=CC(=C(C=C1)C1(CNC1)O)Cl Chemical compound [Si](C)(C)(C(C)(C)C)OC1=CC(=C(C=C1)C1(CNC1)O)Cl UTQCHRYALQNQDS-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 230000009692 acute damage Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002593 adenosine A3 receptor agonist Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- LGHSQOCGTJHDIL-UTXLBGCNSA-N alamethicin Chemical compound N([C@@H](C)C(=O)NC(C)(C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)NC(C)(C)C(=O)N[C@H](C(=O)NC(C)(C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NC(C)(C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NC(C)(C)C(=O)NC(C)(C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](CO)CC=1C=CC=CC=1)C(C)C)C(=O)C(C)(C)NC(=O)[C@@H]1CCCN1C(=O)C(C)(C)NC(C)=O LGHSQOCGTJHDIL-UTXLBGCNSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 108091005466 amylin receptors Proteins 0.000 description 1
- 239000000400 angiotensin II type 1 receptor blocker Substances 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 229960003277 atazanavir Drugs 0.000 description 1
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 1
- 230000000386 athletic effect Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- XPRVSYXHPUYSGF-UHFFFAOYSA-N azetidin-3-one Chemical compound O=C1CNC1 XPRVSYXHPUYSGF-UHFFFAOYSA-N 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 229950010582 betaine anhydrous Drugs 0.000 description 1
- 102000030904 bile acid binding Human genes 0.000 description 1
- 108091022863 bile acid binding Proteins 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 1
- 229960001058 bupropion Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000003293 cardioprotective effect Effects 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000001989 choleretic effect Effects 0.000 description 1
- 230000009693 chronic damage Effects 0.000 description 1
- 230000012085 chronic inflammatory response Effects 0.000 description 1
- 229960001152 colesevelam Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000012969 defense response to bacterium Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 230000013931 endocrine signaling Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002085 enols Chemical group 0.000 description 1
- 230000009483 enzymatic pathway Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- SSQPWTVBQMWLSZ-AAQCHOMXSA-N ethyl (5Z,8Z,11Z,14Z,17Z)-icosapentaenoate Chemical compound CCOC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC SSQPWTVBQMWLSZ-AAQCHOMXSA-N 0.000 description 1
- 229950011259 evogliptin Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 101150001783 fic1 gene Proteins 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229950004781 gemcabene Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 230000036433 growing body Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 210000004024 hepatic stellate cell Anatomy 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 108700012707 hepatitis C virus NS3 Proteins 0.000 description 1
- 208000010710 hepatitis C virus infection Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000004155 insulin signaling pathway Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000007358 intestinal barrier function Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 208000001024 intrahepatic cholestasis Diseases 0.000 description 1
- 230000007872 intrahepatic cholestasis Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- 208000014861 isolated congenital hepatic fibrosis Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 230000005445 isotope effect Effects 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 230000004132 lipogenesis Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000001115 mace Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- RMEDXVIWDFLGES-UHFFFAOYSA-N methyl 6-chloropyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(Cl)N=C1 RMEDXVIWDFLGES-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 108091062762 miR-21 stem-loop Proteins 0.000 description 1
- 108091041631 miR-21-1 stem-loop Proteins 0.000 description 1
- 108091044442 miR-21-2 stem-loop Proteins 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- DDLIGBOFAVUZHB-UHFFFAOYSA-N midazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NC=C2CN=C1C1=CC=CC=C1F DDLIGBOFAVUZHB-UHFFFAOYSA-N 0.000 description 1
- 229960003793 midazolam Drugs 0.000 description 1
- 102000004233 multidrug resistance protein 3 Human genes 0.000 description 1
- 108090000743 multidrug resistance protein 3 Proteins 0.000 description 1
- 238000002552 multiple reaction monitoring Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- MOZRQQTUYAYCQT-FQEVSTJZSA-N n-[[(3s)-3-amino-1-(5-ethyl-7h-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]methyl]-2,4-difluorobenzamide Chemical compound C([C@]1(CCN(C1)C=1N=CN=C2NC=C(C=12)CC)N)NC(=O)C1=CC=C(F)C=C1F MOZRQQTUYAYCQT-FQEVSTJZSA-N 0.000 description 1
- ACFIXJIJDZMPPO-XCSFTKGKSA-N nadph dihydro-nicotinamide-adenine-dinucleotidephosphate Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO[P@](O)(=O)O[P@@](O)(=O)OC[C@H]2[C@@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-XCSFTKGKSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 230000010309 neoplastic transformation Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 229940121308 nidufexor Drugs 0.000 description 1
- JYTIXGYXBIBOMN-UHFFFAOYSA-N nidufexor Chemical compound Cn1nc(C(=O)N(Cc2ccccc2)Cc2ccc(cc2)C(O)=O)c2COc3ccc(Cl)cc3-c12 JYTIXGYXBIBOMN-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- ZXERDUOLZKYMJM-ZWECCWDJSA-N obeticholic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)CCC(O)=O)CC[C@H]21 ZXERDUOLZKYMJM-ZWECCWDJSA-N 0.000 description 1
- 229960001601 obeticholic acid Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000010397 one-hybrid screening Methods 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000014306 paracrine signaling Effects 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 239000002570 phosphodiesterase III inhibitor Substances 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 239000003371 phospholipase C inhibitor Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 1
- 229960003073 pirfenidone Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 201000006038 polycystic kidney disease 4 Diseases 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 208000014081 polyp of colon Diseases 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 208000007232 portal hypertension Diseases 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 108010065251 protein kinase modulator Proteins 0.000 description 1
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 1
- 150000003217 pyrazoles Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000003571 reporter gene assay Methods 0.000 description 1
- 230000001718 repressive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 229950008588 solithromycin Drugs 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- QWCJHSGMANYXCW-UHFFFAOYSA-N sulfaphenazole Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=CC=NN1C1=CC=CC=C1 QWCJHSGMANYXCW-UHFFFAOYSA-N 0.000 description 1
- 229960004818 sulfaphenazole Drugs 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 108091008743 testicular receptors 4 Proteins 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 108091008762 thyroid hormone receptors ß Proteins 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229940121343 tricaprilin Drugs 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229940070126 tropifexor Drugs 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 229960001661 ursodiol Drugs 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- BPQMGSKTAYIVFO-UHFFFAOYSA-N vismodegib Chemical compound ClC1=CC(S(=O)(=O)C)=CC=C1C(=O)NC1=CC=C(Cl)C(C=2N=CC=CC=2)=C1 BPQMGSKTAYIVFO-UHFFFAOYSA-N 0.000 description 1
- 229960004449 vismodegib Drugs 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- XLGQSYUNOIJBNR-UHFFFAOYSA-N vonafexor Chemical compound C=1C=C2OC(C(=O)O)=CC2=C(Cl)C=1N(CC1)CCN1S(=O)(=O)C1=C(Cl)C=CC=C1Cl XLGQSYUNOIJBNR-UHFFFAOYSA-N 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 230000031143 xenobiotic glucuronidation Effects 0.000 description 1
- REQQVBGILUTQNN-UHFFFAOYSA-N ziritaxestat Chemical compound CCC=1N=C2C(C)=CC(N3CCN(CC(=O)N4CC(O)C4)CC3)=CN2C=1N(C)C(SC=1C#N)=NC=1C1=CC=C(F)C=C1 REQQVBGILUTQNN-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201962792714P | 2019-01-15 | 2019-01-15 | |
US62/792,714 | 2019-01-15 | ||
PCT/US2020/013319 WO2020150136A1 (en) | 2019-01-15 | 2020-01-13 | Fxr (nr1h4) modulating compounds |
Publications (1)
Publication Number | Publication Date |
---|---|
CA3124702A1 true CA3124702A1 (en) | 2020-07-23 |
Family
ID=69740522
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA3124702A Pending CA3124702A1 (en) | 2019-01-15 | 2020-01-13 | Fxr (nr1h4) modulating compounds |
Country Status (30)
Country | Link |
---|---|
US (2) | US11225473B2 (ja) |
EP (2) | EP4360632A3 (ja) |
JP (2) | JP7265635B2 (ja) |
KR (1) | KR20210114457A (ja) |
CN (1) | CN113302190A (ja) |
AR (1) | AR117814A1 (ja) |
AU (2) | AU2020209564B2 (ja) |
BR (1) | BR112021011762A2 (ja) |
CA (1) | CA3124702A1 (ja) |
CL (1) | CL2021001877A1 (ja) |
CO (1) | CO2021009240A2 (ja) |
CR (1) | CR20210385A (ja) |
DK (1) | DK3911647T3 (ja) |
DO (2) | DOP2021000148A (ja) |
EA (1) | EA202191566A1 (ja) |
ES (1) | ES2973500T3 (ja) |
FI (1) | FI3911647T3 (ja) |
HR (1) | HRP20240265T1 (ja) |
HU (1) | HUE065889T2 (ja) |
IL (1) | IL284591A (ja) |
LT (1) | LT3911647T (ja) |
MX (1) | MX2021008518A (ja) |
PE (1) | PE20211907A1 (ja) |
PL (1) | PL3911647T3 (ja) |
PT (1) | PT3911647T (ja) |
SG (1) | SG11202107434PA (ja) |
SI (1) | SI3911647T1 (ja) |
TW (1) | TWI733307B (ja) |
WO (1) | WO2020150136A1 (ja) |
ZA (1) | ZA202104705B (ja) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX2018015443A (es) | 2016-06-13 | 2019-04-11 | Gilead Sciences Inc | Compuestos moduladores de fxr (nr1h4). |
CA2968836A1 (en) | 2016-06-13 | 2017-12-13 | Gilead Sciences, Inc. | Fxr (nr1h4) modulating compounds |
JP6906626B2 (ja) | 2017-03-28 | 2021-07-21 | ギリアード サイエンシーズ, インコーポレイテッド | 肝疾患を処置するための治療的組み合わせ |
WO2020081766A1 (en) * | 2018-10-18 | 2020-04-23 | Avolynt | Use of sglt2 inhibitors to treat primary sclerosing cholangitis |
AU2020225225B2 (en) | 2019-02-19 | 2022-12-22 | Gilead Sciences, Inc. | Solid forms of FXR agonists |
JP2023510274A (ja) | 2020-01-15 | 2023-03-13 | アンセルム(アンスティチュート・ナシオナル・ドゥ・ラ・サンテ・エ・ドゥ・ラ・ルシェルシュ・メディカル) | D型肝炎ウイルスによる感染を処置するためのfxrアゴニストの使用 |
US11478533B2 (en) | 2020-04-27 | 2022-10-25 | Novo Nordisk A/S | Semaglutide for use in medicine |
US20220135540A1 (en) * | 2020-10-15 | 2022-05-05 | Eli Lilly And Company | Polymorphs of an fxr agonist |
EP4277630A1 (en) | 2021-01-14 | 2023-11-22 | ENYO Pharma | Method for treating chronic kidney diseases |
MX2023008365A (es) | 2021-01-14 | 2023-10-04 | Enyo Pharma | Efecto sinérgico de un agonista de fxr e ifn para el tratamiento de infección por hbv. |
CA3213217A1 (en) | 2021-04-28 | 2022-11-03 | Raphael Darteil | Strong potentiation of tlr3 agonists effects using fxr agonists as a combined treatment |
TW202311256A (zh) | 2021-06-18 | 2023-03-16 | 美商基利科學股份有限公司 | 用於治療fxr誘發之搔癢之il-31調節劑 |
Family Cites Families (199)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ193011A (en) | 1979-03-19 | 1983-03-15 | Ici Australia Ltd | Diarylamine derivatives intermediates herbicidal compositions |
DE3880544D1 (de) | 1987-04-21 | 1993-06-03 | Basf Ag | P-phenoxy-phenoxymethyl-fuenfring-heteroaromaten. |
JP3121061B2 (ja) | 1991-10-04 | 2000-12-25 | 塩野義製薬株式会社 | アルコキシイミノアセトアミド類製造用中間体の製造法およびそれに用いる中間体 |
DE4137940A1 (de) | 1991-11-18 | 1993-05-19 | Basf Ag | 3-isoxazolylphenylverbindungen, ihre herstellung und ihre verwendung |
US5258551A (en) | 1991-12-18 | 1993-11-02 | Shionogi & Co., Ltd. | Process for producing α-ketoamide derivative |
AU5891494A (en) | 1993-01-29 | 1994-08-15 | Nippon Soda Co., Ltd. | Heterocyclic derivative |
WO1994024095A1 (en) | 1993-04-16 | 1994-10-27 | Abbott Laboratories | Immunosuppressive agents |
IL112721A0 (en) | 1994-03-10 | 1995-05-26 | Zeneca Ltd | Azole derivatives |
CA2195107A1 (en) | 1994-08-02 | 1996-02-15 | Richard Alexander Jelley | Azetidine, pyrrolidine and piperidine derivatives |
GB9501865D0 (en) | 1995-01-31 | 1995-03-22 | Merck Sharp & Dohme | Therapeutic agents |
US5633272A (en) | 1995-02-13 | 1997-05-27 | Talley; John J. | Substituted isoxazoles for the treatment of inflammation |
DE19536811A1 (de) | 1995-10-02 | 1997-04-03 | Basf Ag | Zwischenprodukte und Verfahren zur Herstellung von substituierten Salicylsäurederivaten als Pflanzenschutzmittel |
EP0880363B1 (en) | 1996-02-13 | 2002-09-11 | G.D. SEARLE & CO. | Combinations, having immunosuppressive effects, containing a cyclooxygenase-2 inhibitor and a leukotriene a 4 hydrolase inhibitor |
US6639078B1 (en) | 1998-12-23 | 2003-10-28 | Smithkline Beecham Corporation | Assays for ligands for nuclear receptors |
BR0011741A (pt) | 1999-06-11 | 2002-03-19 | Allergan Sales Inc | Compostos de organossilila tendo atividade de modulação do receptor de hormÈnio nuclear |
US7022725B2 (en) | 2000-11-17 | 2006-04-04 | Takeda Pharmaceutical Company Limited | Isoxazole derivatives |
US20040105885A1 (en) | 2001-04-17 | 2004-06-03 | Ping Gao | Gelatin capsule exhibiting reduced cross-linking |
US20040105883A1 (en) | 2001-04-17 | 2004-06-03 | Ping Gao | Pharmaceutical dosage form capable of maintaining stable dissolution profile upon storage |
US20040105884A1 (en) | 2001-04-17 | 2004-06-03 | Ping Gao | Pharmaceutical dosage form comprising a sulfite compound |
US20040131670A1 (en) | 2001-04-17 | 2004-07-08 | Ping Gao | Pellicle-resistant gelatin capsule |
WO2003000249A1 (fr) | 2001-06-26 | 2003-01-03 | Takeda Chemical Industries, Ltd. | Regulateur de la fonction du recepteur relatif aux retinoides |
EP1423113A4 (en) | 2001-08-13 | 2007-04-18 | Phenex Pharmaceuticals Ag | NR1H4 NUCLEAR RECEPTOR BINDING COMPOUNDS |
US20070010562A1 (en) | 2001-08-13 | 2007-01-11 | Ulrike Bauer | Nr1h4 nuclear receptor binding compounds |
EP1285914B1 (en) | 2001-08-13 | 2007-12-19 | PheneX Pharmaceuticals AG | Nr1h4 nuclear receptor binding compounds |
AU2003225903A1 (en) | 2002-03-21 | 2003-10-08 | Curagen Corporation | Methods of using farnesoid x receptor (fxr) agonists |
US7595311B2 (en) | 2002-05-24 | 2009-09-29 | Exelixis, Inc. | Azepinoindole derivatives as pharmaceutical agents |
US20040132726A1 (en) | 2002-08-09 | 2004-07-08 | Astrazeneca Ab And Nps Pharmaceuticals, Inc. | New compounds |
TWI341314B (en) | 2002-08-09 | 2011-05-01 | Astrazeneca Ab | New compounds |
US7074809B2 (en) | 2002-08-09 | 2006-07-11 | Astrazeneca Ab | Compounds |
EP1407774A1 (en) | 2002-09-10 | 2004-04-14 | LION Bioscience AG | 2-Amino-4-quinazolinones as LXR nuclear receptor binding compounds |
AU2003290796A1 (en) | 2002-11-14 | 2004-06-15 | The Scripps Research Institute | Non-steroidal fxr agonists |
US20050143449A1 (en) | 2002-11-15 | 2005-06-30 | The Salk Institute For Biological Studies | Non-steroidal farnesoid X receptor modulators and methods for the use thereof |
US7319109B2 (en) | 2002-11-22 | 2008-01-15 | Smith Kline Beecham Corporation | Farnesoid X receptor agonists |
US20070166710A1 (en) | 2003-03-31 | 2007-07-19 | Markus Stoffel | Methods for inhibiting adipogenesis and for treating type 2 diabetes |
WO2005077373A2 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Treatment of gastro-esophageal reflux disease (gerd) |
WO2005077345A1 (en) | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Compounds for the treatment of gastro-esophageal reflux disease |
US7585881B2 (en) | 2004-02-18 | 2009-09-08 | Astrazeneca Ab | Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
RU2408589C2 (ru) | 2004-05-14 | 2011-01-10 | Айрм Ллк | Соединения и композиции в качестве модуляторов ppar-рецепторов, активируемых пролифератором пероксисом |
MY144903A (en) | 2004-06-17 | 2011-11-30 | Novartis Ag | Pyrrolopyridine derivatives and their use as crth2 antagonists |
MX2007004484A (es) | 2004-10-13 | 2007-06-25 | Ptc Therapeutics Inc | Compuestos de pirazol o triazol y su uso para la fabricacion de un medicamento para tratar las enfermedades relacionadas con la mutacion somatica. |
JP2008137894A (ja) | 2005-03-22 | 2008-06-19 | Nippon Kayaku Co Ltd | 新規なアセチレン誘導体 |
TW200716576A (en) | 2005-06-07 | 2007-05-01 | Shionogi & Co | Heterocyclic derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
AU2006325815B2 (en) | 2005-12-15 | 2012-07-05 | Exelixis, Inc. | Azepinoindole derivatives as pharmaceutical agents |
JP5081161B2 (ja) | 2005-12-19 | 2012-11-21 | スミスクライン ビーチャム コーポレーション | ファルネソイドx受容体アゴニスト |
US7560551B2 (en) | 2006-01-23 | 2009-07-14 | Amgen Inc. | Aurora kinase modulators and method of use |
CA2640476A1 (en) | 2006-02-03 | 2007-08-16 | Eli Lilly And Company | Compounds and methods for modulating fx-receptors |
CA2642220A1 (en) | 2006-02-14 | 2007-08-23 | Intercept Pharmaceuticals, Inc. | Bile acid derivatives as fxr ligands for the prevention or treatment of fxr-mediated diseases or conditions |
US20070276050A1 (en) | 2006-02-27 | 2007-11-29 | Gilead Sciences, Inc. | Methods for identifying ASK1 inhibitors useful for preventing and/or treating cardiovascular diseases |
WO2007110237A2 (en) | 2006-03-28 | 2007-10-04 | Novartis Ag | Amide derivatives and their application for the treatment of g protein related diseases |
EP2007759A4 (en) | 2006-04-17 | 2010-12-22 | Neuromed Pharmaceuticals Ltd | ISOXAZOLE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS |
CA2651373A1 (en) | 2006-05-24 | 2007-12-06 | Eli Lilly And Company | Compounds and methods for modulating fxr |
EP2029600B1 (de) | 2006-05-24 | 2012-03-14 | Boehringer Ingelheim International GmbH | Substituierte pteridine, die mit einem viergliedrigen heterocyclus substituiert sind |
MX2008014854A (es) | 2006-05-24 | 2008-12-05 | Lilly Co Eli | Antagonistas de fxr. |
ES2523591T3 (es) | 2006-06-27 | 2014-11-27 | Intercept Pharmaceuticals Inc. | Derivados de ácidos biliares como ligandos de FXR para la prevención o el tratamiento de enfermedades o estados mediados por FXR |
CA2656290A1 (en) | 2006-07-05 | 2008-01-10 | Exelixis, Inc. | Methods of using igf1r and abl kinase modulators |
WO2008013660A2 (en) | 2006-07-07 | 2008-01-31 | Biostratum, Inc. | Inhibitors of advanced glycation end products |
JP5153773B2 (ja) | 2006-07-07 | 2013-02-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | フェニル置換ヘテロアリール誘導体及び抗癌剤としてのその使用 |
EP1894924A1 (en) | 2006-08-29 | 2008-03-05 | Phenex Pharmaceuticals AG | Heterocyclic FXR binding compounds |
EP1894928A1 (en) | 2006-08-29 | 2008-03-05 | PheneX Pharmaceuticals AG | Heterocyclic fxr binding compounds |
US8193225B2 (en) | 2006-10-13 | 2012-06-05 | The Board Of Regents Of The University Of Texas System | Isoxazole amides, derivatives and methods of chemical induction of neurogenesis |
CL2007003035A1 (es) | 2006-10-24 | 2008-05-16 | Smithkline Beechman Corp | Compuestos derivados de isoxazol sustituidos, agonistas de receptores farnesoid x; procedimiento de preparacion; composicion farmaceutica que lo comprende; y uso del compuesto en el tratamiento de la obesidad, diabetes mellitus, fibrosis en organos, |
US8501933B2 (en) | 2006-11-09 | 2013-08-06 | Roche Palo Alto Llc | Thiazole and oxazole-substituted arylamides as P2X3 and P2X2/3 antagonists |
EP2121621B1 (en) | 2006-12-08 | 2014-05-07 | Exelixis Patent Company LLC | Lxr and fxr modulators |
GB0625842D0 (en) | 2006-12-22 | 2007-02-07 | Argenta Discovery Ltd | Indolizine derivatives |
US20090105251A1 (en) | 2007-01-25 | 2009-04-23 | Benjamin Jones | Renin inhibitors |
CA2676700C (en) | 2007-02-09 | 2013-12-17 | Dow Agrosciences Llc | Process for the oxidation of certain substituted sulfilimines to insecticidal sulfoximines |
US7511149B2 (en) | 2007-02-09 | 2009-03-31 | Dow Agrosciences Llc | Process for the oxidation of certain substituted sulfilimines to insecticidal sulfoximines |
CA2678028C (en) | 2007-02-26 | 2015-02-03 | Dow Agrosciences Llc | Process for the preparation of certain substituted sulfilimines |
CA2689980A1 (en) | 2007-06-13 | 2008-12-24 | Glaxosmithkline Llc | Farnesoid x receptor agonists |
JP2008308448A (ja) | 2007-06-15 | 2008-12-25 | Sankyo Agro Kk | (3−硫黄原子置換フェニル)へテロアリール誘導体 |
WO2008155054A1 (en) | 2007-06-20 | 2008-12-24 | F. Hoffmann-La Roche Ag | Farnesoid-x-receptor mutants, and crystallisation thereof |
AU2008270784A1 (en) | 2007-07-02 | 2009-01-08 | Glaxosmithkline Llc | Farnesoid X receptor agonists |
JP2010531850A (ja) | 2007-07-02 | 2010-09-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規化合物 |
TW200920372A (en) | 2007-07-13 | 2009-05-16 | Genelabs Tech Inc | Anti-viral compounds, compositions, and methods of use |
US20090197880A1 (en) | 2007-07-13 | 2009-08-06 | Genelabs Technologies, Inc. | Anti-viral compounds, compositions, and methods of use |
TW200906823A (en) | 2007-07-16 | 2009-02-16 | Lilly Co Eli | Compounds and methods for modulating FXR |
MX2010001171A (es) | 2007-08-01 | 2010-03-01 | Lundbeck & Co As H | Uso de abridores de canales de potasio kcnq para reducir los sintomas o tratar desordenes o afecciones en las cuales se encuentra anulado el sistema dopaminergico. |
US8188080B2 (en) | 2007-10-17 | 2012-05-29 | Sanford-Burnham Medical Research Institute | VHR protein tyrosine phosphatase inhibitors, compositions and methods of use |
US20090143451A1 (en) | 2007-11-14 | 2009-06-04 | Andrews William H | Compounds that increase telomerase reverse transcriptase (tert) expression and methods for using the same |
BRPI0821676A2 (pt) | 2007-12-21 | 2015-06-16 | Astrazeneca Ab | Composto, composição farmacêutica, e, processo para a preparação dos compostos. |
EP2110374A1 (en) | 2008-04-18 | 2009-10-21 | Merck Sante | Benzofurane, benzothiophene, benzothiazol derivatives as FXR modulators |
US20120015988A1 (en) | 2008-05-13 | 2012-01-19 | Boehringer Ingelheim International Gmbh | Sulfone Compounds Which Modulate The CB2 Receptor |
US8158636B2 (en) | 2008-05-19 | 2012-04-17 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
JP2011521916A (ja) | 2008-05-19 | 2011-07-28 | バーナム インスティテュート フォー メディカル リサーチ | 腸アルカリホスファターゼモジュレーターおよびそれの使用 |
EP2128158A1 (en) | 2008-05-26 | 2009-12-02 | Phenex Pharmaceuticals AG | Heterocyclic cyclopropyl-substituted FXR binding compounds |
CN104530052A (zh) | 2008-06-10 | 2015-04-22 | 普莱希科公司 | 用于激酶调节的5h-吡咯[2,3-b]吡嗪衍生物和其适应症 |
US8822513B2 (en) | 2010-03-01 | 2014-09-02 | Gtx, Inc. | Compounds for treatment of cancer |
WO2009156336A1 (en) | 2008-06-23 | 2009-12-30 | Basf Se | Sulfoximinamide compounds for combating animal pests |
US20100029655A1 (en) | 2008-07-11 | 2010-02-04 | Martin Robert Leivers | Processes For The Preparation Of Anti-Viral Compounds And Compositions Containing Them |
EP2318381A1 (en) | 2008-08-25 | 2011-05-11 | Dow Global Technologies LLC | Process for preparing isoxazole compounds |
US20120021519A1 (en) | 2008-09-19 | 2012-01-26 | Presidents And Fellows Of Harvard College | Efficient induction of pluripotent stem cells using small molecule compounds |
WO2010034649A1 (en) | 2008-09-25 | 2010-04-01 | F. Hoffmann-La Roche Ag | 2,3-substituted indazole or 4,5,6,7-tetrahydro-indazoles as fxr modulators against dyslipidemia and related diseases |
ES2443947T3 (es) | 2008-09-25 | 2014-02-21 | F. Hoffmann-La Roche Ag | Derivados de 3-amino-indazol o de 3-amino-4,5,6,7-tetrahidro-indazol |
WO2010036362A1 (en) | 2008-09-26 | 2010-04-01 | Wyeth | 1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate nuclear receptor inhibitors |
JP2012506386A (ja) | 2008-10-21 | 2012-03-15 | メタボレックス, インコーポレイテッド | アリールgpr120受容体アゴニストおよびその使用 |
WO2010089303A1 (en) | 2009-02-04 | 2010-08-12 | Boehringer Ingelheim International Gmbh | CYCLIC INHIBITORS OF 11 β-HYDROXYSTEROID DEHYDROGENASE 1 |
WO2010093191A2 (en) | 2009-02-13 | 2010-08-19 | Lg Life Sciences Ltd. | Novel compounds effective as xanthine oxidase inhibitors, method for preparing the same, and pharmaceutical composition containing the same |
FR2943059A1 (fr) | 2009-03-16 | 2010-09-17 | Sanofi Aventis | Derives de n-°6-aza-bicyclo°3.2.1!oct-5-yl)-aryl-methyl!- heterobenzamide,leur preparation et leur application en therapeutique |
JP2012532175A (ja) | 2009-07-06 | 2012-12-13 | ビーエーエスエフ ソシエタス・ヨーロピア | 無脊椎動物系害虫防除用ピリダジン化合物 |
US8883832B2 (en) | 2009-07-06 | 2014-11-11 | Aerpio Therapeutics Inc. | Compounds, compositions, and methods for preventing metastasis of cancer cells |
TWI625121B (zh) | 2009-07-13 | 2018-06-01 | 基利科學股份有限公司 | 調節細胞凋亡信號之激酶的抑制劑 |
JP2013500246A (ja) | 2009-07-24 | 2013-01-07 | ビーエーエスエフ ソシエタス・ヨーロピア | 無脊椎動物系害虫防除用ピリジン誘導体化合物 |
US9212177B2 (en) | 2009-08-05 | 2015-12-15 | Versitech Limited | Antiviral compounds and methods of making and using thereof |
EP2289883A1 (en) | 2009-08-19 | 2011-03-02 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
AU2010291834A1 (en) | 2009-09-04 | 2012-03-15 | Zalicus Pharmaceuticals Ltd. | Substituted heterocyclic derivatives for the treatment of pain and epilepsy |
WO2011047129A1 (en) | 2009-10-15 | 2011-04-21 | Southern Research Institute | Treatment of neurodegenerative diseases, causation of memory enhancement, and assay for screening compounds for such |
WO2011109059A1 (en) | 2010-03-01 | 2011-09-09 | Gtx, Inc. | Compounds for treatment of cancer |
EP2580213A4 (en) | 2010-06-09 | 2013-12-25 | Afraxis Holdings Inc | 8- (HETEROARYLMETHYL) PYRIDO [2,3-D] PYRIMIDIN-7 (8H) -ONES FOR THE TREATMENT OF CNS DISORDERS |
WO2012058531A2 (en) | 2010-10-29 | 2012-05-03 | North Carolina State University | Modulation of response regulators by imidazole derivatives |
TWI408128B (zh) | 2010-12-03 | 2013-09-11 | Nat Univ Tsing Hua | 間-三聯苯衍生物及其在有機發光二極體之應用 |
CU24152B1 (es) | 2010-12-20 | 2016-02-29 | Irm Llc | 1,2 oxazol-8-azabiciclo[3,2,1]octano 8 il como moduladores de fxr |
CN103391937A (zh) | 2010-12-20 | 2013-11-13 | Irm责任有限公司 | 用于调控法尼醇x受体的组合物和方法 |
JP2014500318A (ja) | 2010-12-20 | 2014-01-09 | アイアールエム・リミテッド・ライアビリティ・カンパニー | ファルネソイドx受容体を調節するための組成物および方法 |
EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
WO2013037482A1 (en) | 2011-09-15 | 2013-03-21 | Phenex Pharmaceuticals Ag | Farnesoid x receptor agonists for cancer treatment and prevention |
UA123760C2 (uk) | 2011-11-11 | 2021-06-02 | Гіліад Аполло, Ллс | Сполука (варіанти) та композиція, що містить сполуку |
UY34573A (es) | 2012-01-27 | 2013-06-28 | Gilead Sciences Inc | Inhibidor de la quinasa que regula la señal de la apoptosis |
NZ734451A (en) | 2012-06-19 | 2018-12-21 | Intercept Pharmaceuticals Inc | Preparation, uses and solid forms of obeticholic acid |
TWI621618B (zh) | 2013-03-13 | 2018-04-21 | 比利時商健生藥品公司 | 經取代2-氮雜雙環類及其作為食慾素受體調控劑之用途 |
WO2014181287A1 (en) | 2013-05-09 | 2014-11-13 | Piramal Enterprises Limited | Heterocyclyl compounds and uses thereof |
CN105358154A (zh) | 2013-05-10 | 2016-02-24 | 尼普斯阿波罗有限公司 | Acc抑制剂和其用途 |
SI3360882T1 (sl) | 2013-05-14 | 2021-06-30 | Intercept Pharmaceuticals, Inc. | 11-hidroksil-6-substituirani derivati žolčnih kislin in aminokislinski konjugati le-teh kot modulatorji receptorja farnezoid X |
NZ716568A (en) | 2013-08-01 | 2021-07-30 | Us Health | Inhibitors of the farnesoid x receptor and uses in medicine |
JP6366721B2 (ja) | 2013-09-11 | 2018-08-01 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | B型肝炎ウイルス感染症を処置するための方法及び医薬組成物 |
US20150082981A1 (en) | 2013-09-20 | 2015-03-26 | E I Du Pont De Nemours And Company | Capture of trifluoromethane using ionic liquids |
CN104513213A (zh) | 2013-09-28 | 2015-04-15 | 山东亨利医药科技有限责任公司 | Fxr激动剂 |
WO2015065983A1 (en) | 2013-10-29 | 2015-05-07 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of gastrointestinal infections |
UY35818A (es) | 2013-11-05 | 2015-05-29 | Irm Llc | Composiciones y métodos para modular los receptores x farnesoides |
WO2015116856A2 (en) | 2014-01-29 | 2015-08-06 | City Of Hope | Farnesoid x receptor antagonists |
US10077268B2 (en) | 2014-03-13 | 2018-09-18 | Salk Institute For Biological Studies | FXR agonists and methods for making and using |
JP2017511304A (ja) | 2014-03-13 | 2017-04-20 | ソーク インスティチュート フォー バイオロジカル スタディーズ | フェキサラミン類似体ならびに作製方法および使用方法 |
EP3116878A4 (en) | 2014-03-13 | 2018-02-14 | Salk Institute for Biological Studies | Fxr agonists and methods for making and using |
PE20161366A1 (es) | 2014-04-14 | 2017-01-15 | Gruenenthal Chemie | Heterociclil-sulfonas sustituidas con heteroarilo |
WO2015162538A1 (en) | 2014-04-21 | 2015-10-29 | Lupin Limited | Heterocyclic compounds as calcium sensing receptor modulators for the treatment of hyperparathyroidism, chronic renal failure and chronic kidney disease |
WO2015162244A1 (en) | 2014-04-25 | 2015-10-29 | Basf Se | N-acylamidine compounds |
WO2015165960A1 (en) | 2014-04-30 | 2015-11-05 | Basf Se | N-acylamidine compounds |
DK3626725T3 (da) | 2014-05-29 | 2023-02-27 | Bar Pharmaceuticals S R L | Cholan-derivater til anvendelse ved behandlingen og/eller forebyggelsen af fxr- og tgr5/gpbar1-medierede sygdomme |
CN104045635A (zh) | 2014-06-23 | 2014-09-17 | 华东理工大学 | 3,4,5-三取代异恶唑类化合物及其用途 |
WO2016054560A1 (en) | 2014-10-02 | 2016-04-07 | Flatley Discovery Lab | Isoxazole compounds and methods for the treatment of cystic fibrosis |
EP3006939A1 (en) | 2014-10-06 | 2016-04-13 | Gilead Sciences, Inc. | Histidine-rich Glycoprotein as a marker for hepatic Farnesoid X receptor activation |
TWI577070B (zh) | 2014-10-27 | 2017-04-01 | Lg 化學股份有限公司 | 有機電致發光元件 |
AU2015343025A1 (en) | 2014-11-06 | 2017-06-08 | Enanta Pharmaceuticals, Inc. | Bile acid analogs an FXR/TGR5 agonists and methods of use thereof |
AU2015349687B2 (en) | 2014-11-21 | 2020-07-09 | Akarna Therapeutics, Ltd. | Fused bicyclic compounds for the treatment of disease |
WO2016086115A1 (en) | 2014-11-26 | 2016-06-02 | Enanta Pharmaceuticals, Inc. | Tetrazole derivatives of bile acids as fxr/tgr5 agonists and methods of use thereof |
WO2016086134A1 (en) | 2014-11-26 | 2016-06-02 | Enanta Pharmaceuticals, Inc. | Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof |
US10208081B2 (en) | 2014-11-26 | 2019-02-19 | Enanta Pharmaceuticals, Inc. | Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof |
JP2017535570A (ja) | 2014-11-26 | 2017-11-30 | エナンタ ファーマシューティカルズ インコーポレイテッド | Fxr/tgr5アゴニストとしての胆汁酸類似体およびその使用方法 |
EP3034499A1 (en) | 2014-12-17 | 2016-06-22 | Gilead Sciences, Inc. | Novel FXR (NR1H4) modulating compounds |
EP3034501A1 (en) | 2014-12-17 | 2016-06-22 | Gilead Sciences, Inc. | Hydroxy containing FXR (NR1H4) modulating compounds |
AU2015365481B2 (en) | 2014-12-18 | 2018-08-09 | Novartis Ag | Azabicyclooctane derivatives as FXR agonists for use in the treatment of liver and gastrointestinal diseases |
EA201892625A1 (ru) | 2015-01-09 | 2019-07-31 | Джилид Аполло, Ллс | КОМБИНИРОВАННАЯ ТЕРАПИЯ С ПРИМЕНЕНИЕМ ИНГИБИТОРА АЦЕТИЛ-КоА-КАРБОКСИЛАЗЫ (ACC) ДЛЯ ЛЕЧЕНИЯ НЕАЛКОГОЛЬНОЙ ЖИРОВОЙ БОЛЕЗНИ ПЕЧЕНИ |
US10597364B2 (en) | 2015-01-20 | 2020-03-24 | Boehringer Ingelheim Animal Health USA Inc. | Anthelmintic compounds, compositions and method of using thereof |
TWI698430B (zh) | 2015-02-13 | 2020-07-11 | 南北兄弟藥業投資有限公司 | 三環化合物及其在藥物中的應用 |
US10100285B2 (en) | 2015-04-03 | 2018-10-16 | Propagenix Inc. | Ex vivo proliferation of epithelial cells |
CN106146483A (zh) | 2015-04-23 | 2016-11-23 | 上海迪诺医药科技有限公司 | 杂环类法尼酯衍生物x受体调节剂 |
GB201507340D0 (en) | 2015-04-29 | 2015-06-10 | Univ St Andrews | Light emitting devices and compounds |
CN107920523A (zh) | 2015-07-13 | 2018-04-17 | 范德比尔特大学 | Orco激动剂的热挥发 |
DK3347450T3 (da) | 2015-09-11 | 2021-05-31 | Propagenix Inc | Ex vivo-proliferation af epithelceller |
AR106948A1 (es) | 2015-12-04 | 2018-03-07 | Bristol Myers Squibb Co | Agonistas del receptor de apelina y método de uso |
TW201734002A (zh) | 2015-12-11 | 2017-10-01 | 拜耳作物科學股份有限公司 | 作為殺蟲劑之經取代的丙二醯胺類 |
CN106946867B (zh) | 2016-01-06 | 2019-11-12 | 广州市恒诺康医药科技有限公司 | Fxr受体调节剂及其制备方法和用途 |
EP3190103A1 (en) | 2016-01-08 | 2017-07-12 | Rijksuniversiteit Groningen | Inhibitors of the pd-1/pd-l1 protein/protein interaction |
US10882871B2 (en) | 2016-01-10 | 2021-01-05 | British Columbia Cancer Agency Branch | 18/19F-labelled compounds which target the prostate specific membrane antigen |
WO2017122209A2 (en) | 2016-01-12 | 2017-07-20 | Yeda Research And Development Co. Ltd. | NF-kappaB INHIBITORS |
WO2017128896A1 (zh) | 2016-01-26 | 2017-08-03 | 江苏豪森药业集团有限公司 | Fxr激动剂及其制备方法和应用 |
CN107021957A (zh) | 2016-02-01 | 2017-08-08 | 山东轩竹医药科技有限公司 | Fxr受体激动剂 |
CN107021958A (zh) | 2016-02-01 | 2017-08-08 | 山东轩竹医药科技有限公司 | Fxr受体激动剂 |
WO2017133521A1 (zh) | 2016-02-01 | 2017-08-10 | 山东轩竹医药科技有限公司 | Fxr受体激动剂 |
TW201741307A (zh) | 2016-02-22 | 2017-12-01 | 艾洛斯生物製藥公司 | Fxr調節劑及其使用方法 |
CN107224583A (zh) | 2016-03-24 | 2017-10-03 | 中美华世通生物医药科技(武汉)有限公司 | 药物组合物及其用途 |
WO2017189652A1 (en) | 2016-04-26 | 2017-11-02 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as fxr agonists and methods of use thereof |
US10080743B2 (en) | 2016-04-26 | 2018-09-25 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as FXR agonists and methods of use thereof |
WO2017189651A1 (en) | 2016-04-26 | 2017-11-02 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as fxr agonists and methods of use thereof |
WO2017201152A1 (en) | 2016-05-18 | 2017-11-23 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as fxr agonists and methods of use thereof |
WO2017201155A1 (en) | 2016-05-18 | 2017-11-23 | Enanta Pharmaceuticals, Inc. | lSOXAZOLE DERIVATIVES AS FXR AGONISTS AND METHODS OF USE THEREOF |
US10144729B2 (en) | 2016-05-18 | 2018-12-04 | Enanta Pharmaceuticals, Inc. | Isoxazole analogs as FXR agonists and methods of use thereof |
CN115154467A (zh) | 2016-06-03 | 2022-10-11 | 坎莫森特里克斯公司 | 治疗肝纤维化的方法 |
MX2018015483A (es) | 2016-06-13 | 2019-03-18 | Glaxosmithkline Ip Dev Ltd | Piridinas sustituidas como inhibidores de adn metiltransferasa-1 (dnmt1). |
MX2018015443A (es) * | 2016-06-13 | 2019-04-11 | Gilead Sciences Inc | Compuestos moduladores de fxr (nr1h4). |
CA2968836A1 (en) | 2016-06-13 | 2017-12-13 | Gilead Sciences, Inc. | Fxr (nr1h4) modulating compounds |
AR108711A1 (es) | 2016-06-13 | 2018-09-19 | Gilead Sciences Inc | Compuestos moduladores de fxr (nr1h4) |
TW201808283A (zh) | 2016-08-05 | 2018-03-16 | 廣東東陽光藥業有限公司 | 含氮三環化合物及其在藥物中的應用 |
MA46052A (fr) | 2016-08-23 | 2021-03-17 | Ardelyx Inc | Modulateurs du récepteur hormonal pour le traitement d'états et de troubles métaboliques |
US11091482B2 (en) | 2016-08-23 | 2021-08-17 | Ardelyx, Inc. | Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators |
CN108430998B (zh) | 2016-09-28 | 2021-07-09 | 四川科伦博泰生物医药股份有限公司 | 氮杂双环衍生物及其制备方法和用途 |
EP3519408A1 (en) | 2016-09-29 | 2019-08-07 | Bayer CropScience Aktiengesellschaft | 1 -[2-(1 -chlorocyclopropyl)-2-hydroxy-3-(3-phenyl-1,2-oxazol-5-yl)propyl]-1h-imidazole-5-carbonitrile derivatives and related compounds as fungicides for crop protection |
US10450306B2 (en) | 2016-10-04 | 2019-10-22 | Enanta Pharmaceuticals, Inc. | Isoxazole analogs as FXR agonists and methods of use thereof |
KR20190109387A (ko) * | 2016-10-18 | 2019-09-25 | 마드리갈 파마슈티칼스, 인크. | Thr-베타 아고니스트로 간 질환 또는 지질 질환을 치료하는 방법 |
CN107973790A (zh) | 2016-10-22 | 2018-05-01 | 合帕吉恩治疗公司 | 杂环fxr调节剂 |
KR20190083659A (ko) | 2016-11-10 | 2019-07-12 | 갈메드 리서치 앤드 디벨롭먼트 리미티드 | 섬유증에 대한 치료 |
CA3042398A1 (en) * | 2016-11-11 | 2018-05-17 | Gilead Sciences, Inc. | Methods of treating liver disease |
CN106588804B (zh) | 2016-12-09 | 2018-11-09 | 都创(上海)医药科技有限公司 | 一种作为类法尼醇x受体(fxr)的化合物的制备方法 |
CN106632294A (zh) | 2016-12-15 | 2017-05-10 | 宁波百纳西药业有限公司 | 一种螺环化合物及其药物用途 |
CN106748922B (zh) | 2017-01-12 | 2019-02-01 | 中国药科大学 | 一类新型砜酸衍生物、其制备方法及其作为药物的用途 |
JP6906626B2 (ja) | 2017-03-28 | 2021-07-21 | ギリアード サイエンシーズ, インコーポレイテッド | 肝疾患を処置するための治療的組み合わせ |
TW201902478A (zh) | 2017-04-12 | 2019-01-16 | 美商基利科學股份有限公司 | 治療肝臟疾病之方法 |
WO2018190643A1 (en) | 2017-04-12 | 2018-10-18 | Il Dong Pharmaceutical Co., Ltd. | An isoxazole derivatives as nuclear receptor agonists and used thereof |
AU2020225225B2 (en) | 2019-02-19 | 2022-12-22 | Gilead Sciences, Inc. | Solid forms of FXR agonists |
WO2020185686A1 (en) | 2019-03-11 | 2020-09-17 | Gilead Sciences, Inc. | Formulations of a compound and uses thereof |
-
2020
- 2020-01-13 BR BR112021011762A patent/BR112021011762A2/pt unknown
- 2020-01-13 US US16/741,101 patent/US11225473B2/en active Active
- 2020-01-13 PL PL20708721.4T patent/PL3911647T3/pl unknown
- 2020-01-13 ES ES20708721T patent/ES2973500T3/es active Active
- 2020-01-13 FI FIEP20708721.4T patent/FI3911647T3/fi active
- 2020-01-13 SI SI202030376T patent/SI3911647T1/sl unknown
- 2020-01-13 KR KR1020217025511A patent/KR20210114457A/ko active IP Right Grant
- 2020-01-13 SG SG11202107434PA patent/SG11202107434PA/en unknown
- 2020-01-13 EP EP23215648.9A patent/EP4360632A3/en active Pending
- 2020-01-13 CR CR20210385A patent/CR20210385A/es unknown
- 2020-01-13 JP JP2021540517A patent/JP7265635B2/ja active Active
- 2020-01-13 LT LTEPPCT/US2020/013319T patent/LT3911647T/lt unknown
- 2020-01-13 HU HUE20708721A patent/HUE065889T2/hu unknown
- 2020-01-13 WO PCT/US2020/013319 patent/WO2020150136A1/en unknown
- 2020-01-13 EP EP20708721.4A patent/EP3911647B1/en active Active
- 2020-01-13 AU AU2020209564A patent/AU2020209564B2/en active Active
- 2020-01-13 EA EA202191566A patent/EA202191566A1/ru unknown
- 2020-01-13 DK DK20708721.4T patent/DK3911647T3/da active
- 2020-01-13 CA CA3124702A patent/CA3124702A1/en active Pending
- 2020-01-13 PE PE2021001167A patent/PE20211907A1/es unknown
- 2020-01-13 HR HRP20240265TT patent/HRP20240265T1/hr unknown
- 2020-01-13 PT PT207087214T patent/PT3911647T/pt unknown
- 2020-01-13 CN CN202080009189.4A patent/CN113302190A/zh active Pending
- 2020-01-13 MX MX2021008518A patent/MX2021008518A/es unknown
- 2020-01-14 TW TW109101217A patent/TWI733307B/zh active
- 2020-01-14 AR ARP200100089A patent/AR117814A1/es unknown
-
2021
- 2021-07-04 IL IL284591A patent/IL284591A/en unknown
- 2021-07-06 ZA ZA2021/04705A patent/ZA202104705B/en unknown
- 2021-07-14 CO CONC2021/0009240A patent/CO2021009240A2/es unknown
- 2021-07-14 CL CL2021001877A patent/CL2021001877A1/es unknown
- 2021-07-14 DO DO2021000148A patent/DOP2021000148A/es unknown
- 2021-11-24 US US17/534,951 patent/US20220204491A1/en active Pending
-
2023
- 2023-02-20 JP JP2023024340A patent/JP2023062120A/ja not_active Withdrawn
- 2023-02-21 AU AU2023200994A patent/AU2023200994A1/en active Pending
- 2023-09-15 DO DO2023000196A patent/DOP2023000196A/es unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2020209564B2 (en) | FXR (NR1H4) modulating compounds | |
AU2020202618B2 (en) | FXR (NR1H4) modulating compounds | |
EP3730487B1 (en) | Azetidine derivatives as fxr (nr1h4) modulators | |
EP3468977B1 (en) | Fxr (nr1h4) modulating compounds | |
EA046251B1 (ru) | Соединения, модулирующие fxr (nr1h4) | |
OA19551A (en) | FXR (NR1H4) modulating compounds. | |
OA20099A (en) | "FXR (NR1H4) modulating compounds". |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request |
Effective date: 20210622 |
|
EEER | Examination request |
Effective date: 20210622 |
|
EEER | Examination request |
Effective date: 20210622 |
|
EEER | Examination request |
Effective date: 20210622 |
|
EEER | Examination request |
Effective date: 20210622 |
|
EEER | Examination request |
Effective date: 20210622 |
|
EEER | Examination request |
Effective date: 20210622 |
|
EEER | Examination request |
Effective date: 20210622 |
|
EEER | Examination request |
Effective date: 20210622 |